Effects of calcium channel blockers on hyaluronidase-induced capillary vascular permeability

Abstract

Inflammation and increased capillary permeability is a significant aspect of the pathogenesis of many diseases including atherosclerosis. L-type calcium channel blockers (CCB) are commonly used as cardiovascular drugs. Amlodipine, lacidipine, and nicardipine were evaluated for anti-inflammatory activity on the paw oedema produced by carrageenan. The effect of these drugs was compared with the activity of indomethacin. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. In our animal experiments, amlodipine decreased the carrageenan-induced paw oedema at doses of 1, 3, and 6 mg kg(-1) by 27.3%, 43.7%, and 67.3% four hour after carrageenan administration; the same doses of lacidipine and nicardipine decreased paw oedema by 37.1%, 55.6%, 76.4%, 11.2%, 31.0%, 91%; and indomethacin decreased oedema by 38.2% at a dose of 6 mg kg(-1). Lacidipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at doses of 1, 3, and 6 mg kg(-1) compared with the control group. However, amlodipine and nicardipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at 3 and 6 mg kg(-1) doses. A 6 mg kg(-1) dose of indomethacin significantly decreased the capillary permeability which was increased by hyaluronidase. These results suggest that CCBs can be efficient anti-inflammatories, and can also significantly decrease capillary permeability.